Abstract
Although superiority of synthetic surfactant over animal-driven surfactant has been known, there is no synthetic surfactant commercially available at present. Many trials have been made to develop synthetic surfactant comparable in function to animal-driven surfactant. The efficacy of treatment with a new synthetic surfactant (CHF5633) containing dipalmitoylphosphatidylcholine, phosphatidylglycerol, SP-B analog, and SP-C analog was evaluated using immature newborn lamb model and compared with animal lung tissue-based surfactant Survanta. Lambs were treated with a clinical dose of 200 mg/kg CHF5633, 100 mg/kg Survanta, or air after 15 min initial ventilation. All the lambs treated with air died of respiratory distress within 90 min of age. During a 5 h study period, Pco2 was maintained at 55 mmHg with 24 cmH2O peak inspiratory pressure for both groups. The preterm newborn lamb lung functions were dramatically improved by CHF5633 treatment. Slight, but significant superiority of CHF5633 over Survanta was demonstrated in tidal volume at 20 min and dynamic lung compliance at 20 and 300 min. The ultrastructure of CHF5633 was large with uniquely aggregated lipid particles. Increased uptake of CHF5633 by alveolar monocytes for catabolism was demonstrated by microphotograph, which might be associated with the higher treatment dose of CHF5633. The higher catabolism of CHF5633 was also suggested by the similar amount of surfactant lipid in bronchoalveolar lavage fluid (BALF) between CHF5633 and Survanta groups, despite the 2-fold higher treatment dose of CHF5633. Under the present ventilation protocol, lung inflammation was minimal for both groups, evaluated by inflammatory cell numbers in BALF and expression of IL-1β, IL-6, IL-8, and TNFα mRNA in the lung tissue. In conclusion, the new synthetic surfactant CHF5633 was effective in treating extremely immature newborn lambs with surfactant deficiency during the 5 h study period.
Highlights
The current commercial surfactants for treatment of preterm newborns with respiratory distress syndrome (RDS) are derived from lung tissue or bronchoalveolar lavage fluid (BALF) of bovine or swine
CHF5633 is the new totally synthetic surfactant synthesized by Chiesi Farmaceutici S.p.A (Parma, Italy) for the treatment of preterm newborn infants with RDS
Preterm Lamb Delivery and Ventilation Lambs delivered at 124d gestational age by Cesarean section were chosen for this study because they were relatively uniform in severity of lung immaturity with surfactant deficiency
Summary
The current commercial surfactants for treatment of preterm newborns with respiratory distress syndrome (RDS) are derived from lung tissue or bronchoalveolar lavage fluid (BALF) of bovine or swine. Use of synthetic surfactant would lower the cost for treatment. CHF5633 is the new totally synthetic surfactant synthesized by Chiesi Farmaceutici S.p.A (Parma, Italy) for the treatment of preterm newborn infants with RDS. SP-C analogue is a 33-amino acid protein formed by both N-terminal segment analog of native SP-C and hydrophobic C-terminal helical segment similar to that of native SP-C. SP-B analogue is a 34-amino acid protein derived from the two parts (8–25 and 63–78) of the full-length natural SP-B. Preliminary unpublished studies with CHF5633 demonstrated high surface activity as well as resistance against surfactant deterioration in vitro and improvement of preterm newborn rabbit lung compliance. CHF5633 is a white uniform suspension, stable at room temperature, has low viscosity, and does not require any heating before use
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